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Background: The exponential expansion of the population, in conjunction with the escalating negative side effects associated with synthetic contraceptives, has prompted the exploration of alternative fertility control agents, particularly those sourced from medicinal plants. Currently, several articles exist on the antifertility properties of medicinal plants. However, the application of a quantitative structured methodology such as bibliometrics to provide insight into this research field is limited. Purpose: In this study, a quantitative analysis of published research articles that have been evaluated plants for their antifertility activities were examined using a bibliometric approach. We focused on publication trends, publishers, authors, keywords, countries, research hotspots, and research gaps. Methods: Data was obtained from Scopus and analysed using RStudio biblioshiny and VOSviewer software. A total of 614 research articles was retrieved after applying the inclusion and exclusion criteria. Results: A downward trend in research in this field was evident. The journal “Contraception”, was the most productive, with 57 publications. Furthermore, there has been a shift in the direction of research, with more focus on male contraception. VOSviewer analysis established India, Nigeria, and Iran as the most productive countries based on the number of publications. In terms of institutions, the University of Rajasthan (India) produced the most articles. The author's keyword analysis resulted in the identification of 10 most studied plants based on keyword frequency. Carica papaya L. was the most studied plant, showing promising male and female antifertility activities. Oestrus cycle analysis, anti-implantation activity, and anti-spermatogenic activities were identified as the major modes of action used by researchers for evaluating plant antifertility activities. Conclusion: We identified various research hotspots, detailing the modes of action used for evaluating plant antifertility activities. Carica papaya L., Azadirachta indica A.Juss., and Momordica charantia L. were the most studied plants and have the potential to be further investigated and developed into herbal contraceptives. Finally, there is a need to isolate compounds present in these plants and determine their antifertility properties in both preclinical and clinical studies.

Objective: Child poverty is associated with poor adolescent mental health. Changes to the Child Tax Credit (CTC) in 2021 in the U.S. were historic and introduced a new model of distributing the credit in advance of tax filing, providing families with stable, supplemental monthly income. This policy shift offers a unique opportunity to examine the mental health effects for adolescents. Methods: We use electronic health record data from a large pediatric primary care network in Columbus, Ohio, which collected adolescent depression screening scores in real time as the CTC advance payments were introduced. We utilized differences in age of eligibility for the CTC to examine the changes in the probability of depression screening outcomes (positive depression screen, any depression symptom, any suicidal ideation), for adolescents eligible for the credit (turned 18 first quarter of 2022), relative to those not eligible (turned 18 last quarter of 2021) (n = 1,423). Results: We did not observe a significant association between the policy change and study outcomes in the overall sample. However, the percentage of adolescents with a positive depression screen significantly declined for Non-Hispanic Black (13.4 percentage point reduction, p = 0.01) and publicly insured (9.7 percentage point reduction, p = 0.04) adolescents. Conclusions: Our findings suggest reductions in depression symptoms for subgroups of adolescents who were age-eligible for the CTC compared to their counterparts who were not eligible. The CTC advance payments were a brief experiment in universal basic income and may offer a policy solution for addressing both poverty and a growing adolescent mental health crisis.

Summary: Background: Long COVID is the patient-coined term for the persistent symptoms of COVID-19 illness for weeks, months or years following the acute infection. There is a large burden of long COVID globally from self-reported data, but the epidemiology, causes and treatments remain poorly understood. Primary care is used to help identify and treat patients with long COVID and therefore Electronic Health Records (EHRs) of past COVID-19 patients could be used to help fill these knowledge gaps. We aimed to describe the incidence and differences in demographic and clinical characteristics in recorded long COVID in primary care records in England. Methods: With the approval of NHS England we used routine clinical data from over 19 million adults in England linked to SARS-COV-2 test result, hospitalisation and vaccination data to describe trends in the recording of 16 clinical codes related to long COVID between November 2020 and January 2023. Using OpenSAFELY, we calculated rates per 100,000 person-years and plotted how these changed over time. We compared crude and adjusted (for age, sex, 9 NHS regions of England, and the dominant variant circulating) rates of recorded long COVID in patient records between different key demographic and vaccination characteristics using negative binomial models. Findings: We identified a total of 55,465 people recorded to have long COVID over the study period, which included 20,025 diagnoses codes and 35,440 codes for further assessment. The incidence of new long COVID records increased steadily over 2021, and declined over 2022. The overall rate per 100,000 person-years was 177.5 cases in women (95% CI: 175.5–179) and 100.5 in men (99.5–102). The majority of those with a long COVID record did not have a recorded positive SARS-COV-2 test 12 or more weeks before the long COVID record. Interpretation: In this descriptive study, EHR recorded long COVID was very low between 2020 and 2023, and incident records of long COVID declined over 2022. Using EHR diagnostic or referral codes unfortunately has major limitations in identifying and ascertaining true cases and timing of long COVID. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

Summary: Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. We aimed to evaluate and estimate the differences in health impacts of long COVID across sociodemographic categories and quantify this in Quality-Adjusted Life-Years (QALYs), widely used measures across health systems. Methods: With the approval of NHS England, we utilised OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID. Findings: The total OpenPROMPT cohort consisted of 7575 individuals who consented to data collection, with which we used data from 6070 participants who completed a baseline research questionnaire where 24.6% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a higher likelihood or odds of reporting loss in quality-of-life (Odds Ratio (OR): 4.7, 95% CI: 3.72–5.93) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 17.7, 95% CI: 10.37–30.33) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss. Interpretation: We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease. Funding: This research was supported by the National Institute for Health and Care Research (NIHR) (OpenPROMPT: COV-LT2-0073).

Summary: Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

There is mounting evidence that cancer patients co-administer herbal drugs with chemotherapy, however, information on the pharmacodynamic (PD) effects of such combination therapy is scarce. Natural products including crude extracts, herbal formulas, and bioactive compounds from plants hold great potential to prevent and treat cancers. More importantly, some herbal drugs can reduce the incidence of chemotherapy-induced toxicity including oral mucositis, gastrointestinal toxicity, hepatotoxicity etc. This review focuses on the effectiveness of some herbal products as adjuvant therapy and describes the possible mechanisms of chemo-herbal drug PD interactions in enhancing the efficacy/ or reducing the side effects of chemotherapy. We also highlighted recent advances in preclinical in vitro and in vivo studies to establish the effectiveness of herbal medicine to enhance efficacy or counteract chemotherapy-induced side effects. In addition, we draw particular attention to the synergistic effects of chemo-herbal drug combination therapy to prevent and treat cancers using evidence from clinical trials. We concluded that herbal drugs hold great potential as adjuvant therapy for the prevention and treatment of chemotherapy-induced side effects. It is important to also highlight that the clinical evidence on chemo-herbal drug combination therapy is limited. There is an urgent need for an in-depth PD evaluation including the safety pharmacology of chemo-herbal drug combination therapy as well as reliable evidence from multicentre clinical trials to establish the beneficial or negative effects of chemo-herbal drug combination therapy in the ongoing fight against cancer.

Summary: We describe a method to silence genes in primary acute myeloid leukemia cells by transducing them with shRNA in lentiviral vectors. The transduction of primary non-adherent cells is particularly challenging. The protocol will aid in performing such experiments and is particularly helpful to prepare cells for in vivo engraftment studies. Use of a special medium supplemented with cytokines preserves the viability of the leukemic stem cells and their ability to engraft the marrow of immune-deficient mice.For complete details on the use and execution of this protocol, please refer to Singh et al. (2020).

The necroptotic effector molecule MLKL accumulates in neurons over the lifespan of mice, and its downregulation has the potential to improve cognition through neuroinflammation, and changes in the abundance of synaptic proteins and enzymes in the central nervous system. Notwithstanding, direct evidence of cell-autonomous effects of MLKL expression on neuronal physiology and metabolism are lacking. Here, we tested whether the overexpression of MLKL in the absence of cell death in the neuronal cell line Neuro-2a recapitulates some of the hallmarks of aging at the cellular level. Using genetically-encoded fluorescent biosensors, we monitored the cytosolic and mitochondrial Ca 2+ levels, along with the cytosolic concentrations of several metabolites involved in energy metabolism (lactate, glucose, ATP) and oxidative stress (oxidized/reduced glutathione). We found that MLKL overexpression marginally decreased cell viability, however, it led to reduced cytosolic and mitochondrial Ca 2+ elevations in response to Ca 2+ influx from the extracellular space. On the contrary, Ca 2+ signals were elevated after mobilizing Ca 2+ from the endoplasmic reticulum. Transient elevations in cytosolic Ca 2+ , mimicking neuronal stimulation, lead to higher lactate levels and lower glucose concentrations in Neuro-2a cells when overexpressing MLKL, which suggest enhanced neuronal glycolysis. Despite these alterations, energy levels and glutathione redox state in the cell bodies remained largely preserved after inducing MLKL overexpression for 24-48 h. Taken together, our proof-of-concept experiments are consistent with the hypothesis that MLKL overexpression in the absence of cell death contributes to both Ca 2+ and metabolic dyshomeostasis, which are cellular hallmarks of brain aging., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Aberration correction combined with a pixelated detector enable atomic-resolution phase-contrast imaging in the scanning transmission electron microscope (STEM) using all elastically scattered electrons within the illumination cone. The review describes this possibility in detail revisiting the image formation in the STEM on a fundamental quantum-mechanical treatment of electron scattering within the object and the effect of the lenses on the electron wave. Describing electron scattering by means of scattering amplitudes enables a straightforward derivation of a) the reciprocity theorem, b) the optical theorem of electron scattering, and c) the precise formulation of the image intensity distribution in the STEM for different modes of operation. The second part of the review describes in detail a novel method for obtaining pure phase-contrast images in the STEM using the integrated differential phase-contrast (IDPC) procedure. The incorporation of a chromatic (Cc) and spherically (Cs) corrected objective lens and a pixelated detector in the STEM combined with numerical through-focusing enables optical sectioning with atomic 3D resolution of thick objects with about the same dose as that for a 2D object, at least in principle. Numerical simulations of the IDPC transfer function and the point spread function for the focal plane and several reconstructed defocused planes demonstrate the feasibility of the method., (Copyright © 2022. Published by Elsevier B.V.)

The realization of chromatic aberration correction enables energy-filtered transmission electron microscopy (EFTEM) at atomic resolution even for large energy windows. Previous works have demonstrated lattice contrast from ionization-edge signals such as the L 2,3 edges of silicon or titanium. However, the direct interpretation as chemical information was found to be hampered by contributions from elastic contrast with dynamic scattering, especially for thick samples. Here we demonstrate that even for thin samples with light atoms, the interpretation of the ionization-edge signal is complicated by inversions from bright-atom to dark-atom contrast. Our EFTEM experiments for graphene show lattice contrast in the carbon K-edge signal, and we find bright-atom and dark-atom contrast for different defoci., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aberration correction in transmission electron microscopy has proven feasible and useful over a large range of acceleration voltages. The spherical aberration has been corrected for beam energies from 15 kV [1] up to 1.2 MeV [2] while the correction of the chromatic aberration has been achieved for beam energies ranging from 20 kV[3] up to 300 kV[4]. Above this threshold the conventional correction principle based on mixed electric and magnetic focusing elements becomes infeasible with present technology [5]. For conventional electron sources at high voltages the relative energy width of the beam gets so small that chromatic correction becomes less important. Nevertheless, for new applications with pulsed electron sources with energy spreads in the order of 100 eV chromatic aberration will become a limiting factor even at high energies [6]. To enable chromatic aberration correction for such systems a novel type of a feasible, purely magnetic multipole aberration corrector with curved optic axis is proposed which is capable of compensating for the chromatic and spherical aberration up to several MeV., (Copyright © 2018. Published by Elsevier B.V.)

Partial coherence of the electron waves leaving the specimen is taken into account in the high-resolution transmission electron microscopy (HRTEM) image simulation by mainly three methods - the incoherent summation approach, the transmission cross-coefficient (TCC) model, and the quasi-coherent model. In the incoherent summation approach, coherent images are calculated for each point in the effective source and summed up incoherently. The TCC is the transfer function of the microscope obtained based on the incoherent summation approach. An analytical form of the TCC can be derived by assuming a Gaussian distribution for the source radiation and for the variation of the focal length caused by the energy spread of the effective source. In the quasi-coherent model, the partial coherence effect is simplified by multiplying the wave function at the diffraction plane with the envelope functions. Envelope functions suppress the contributions to the image contrast from waves which do not propagate along the optical axis. The quasi-coherent model is usually sufficient for the image simulation of weak phase objects. This model is more computationally efficient than both the incoherent summation approach and the TCC model. For the C s -corrected and C c /C s -corrected microscopes operating at 80 kV, we have compared images simulated by using the three models with the experimental images. The comparison shows that the quasi-coherent model also provides a sufficient approximation for the image simulation of high-Z materials if chromatic aberration is corrected and the samples comprise only several atomic layers. In the case of only C s -correction, the incoherent summation approach or the TCC model needs to be employed for modelling the imaging of high-Z samples even though it is more computationally consuming., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The annular differential phase contrast (ADPC) mode in a third-order spherical aberration-corrected scanning transmission electron microscope (STEM) has recently been realized at an operating voltage of 300 kV by inserting a physical Fresnel phase plate in front of the objective lens and by using a detector geometry which matches that of the Fresnel phase plate [1]. By image calculation we explore the feasibility of this mode for the voltage range of 20-80kV. Alternatively, we mimic the Fresnel phase plate material-free with the help of the adjustable aberrations of the corrector. The additional correction of chromatic aberration, fifth-order spherical aberration and image spread improves significantly the resolution and contrast. Under these advanced conditions it is possible to achieve optical sectioning in the ADPC mode with atomic resolution and a depth of field shorter than 3 Å for an accelerating voltage of 30 kV. Moreover, we show that the contrast obtained in the ADPC mode is clearly superior over the contrast in incoherent bright-field (IBF) and high-angle annular dark-field (HAADF), the two other common methods in STEM. We propose that with the advanced ADPC method applied in STEM, the investigation of the inner structure of thick samples will be possible without slicing., (Copyright © 2018. Published by Elsevier B.V.)

Background: During the Vietnam War, many veterans were exposed to Agent Orange (AO), a chemical defoliant containing varying levels of the carcinogen dioxin. The health effects of AO exposure have been widely studied in the VA population. Here we review and interpret data regarding the association between AO exposure and bladder cancer (BC) mortality., Main Findings: Data evaluating the association between AO and BC is limited. Methods characterizing exposure have become more sophisticated over time. Several studies support the link between AO exposure and increased mortality due to BC, including the Korean Veterans Health Study., Conclusions: Available data suggest an association with exposure to AO and increased mortality due to BC. In patients exposed to AO, increased frequency of cystoscopic surveillance and potentially more aggressive therapy for those with BC may be warranted but utility of these strategies remains to be proven. Additional research is required to better understand the relationship between AO and BC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Globally, alcohol use is the leading cause of ill health and life years lost in adolescents, although its clinical impact is often overlooked, particularly in England where most research is based in schools. This study aims to examine the prevalence of alcohol consumption and the association between alcohol consumption and age of onset with health and social consequences among adolescents presenting to emergency departments (EDs)., Methods: Consecutive attenders (n = 5,576) aged 10-17 years at 10 EDs were included. Information was collected on general health and functioning, quality of life, alcohol use, and alcohol-related health and social consequences., Results: Nearly 40% of adolescents reported the consumption of alcohol that was more than a sip in their lifetime. Age of the first alcohol consumption before the age of 15 years was associated with tobacco use (p < .001), lower quality of life (p = .003), and evidence of an alcohol use disorder (p = .002). It was also associated with general social functioning (problems with conduct p = .001 and hyperactivity p = .001) and alcohol-related health and social consequences (accident p = .046, problems with a parent p = .017, school p = .0117, or police p = .012)., Conclusions: Rates of alcohol consumption in adolescents presenting to the ED were similar to those reported in schools in England and globally. Associations of alcohol consumption and earlier onset of drinking with poorer health and social functioning were observed. The ED can offer an opportunity for the identification of hazardous alcohol use in adolescents., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Electron scattering is always applied as one of the routines to investigate nanostructures. Nowadays the development of hardware offers more and more prospect for this technique. For example imaging nanostructures with inelastic scattered electrons may allow to produce component-sensitive images with atomic resolution. Modelling inelastic electron scattering is therefore essential for interpreting these images. The main obstacle to study inelastic scattering problem is its complexity. During inelastic scattering, incident electrons entangle with objects, and the description of this process involves a multidimensional array. Since the simulation usually involves fourdimensional Fourier transforms, the computation is highly inefficient. In this work we have offered one solution to handle the multidimensional problem. By transforming a high dimensional array into twodimensional array, we are able to perform matrix diagonalization and approximate the original multidimensional array with its twodimensional eigenvectors. Our procedure reduces the complicated multidimensional problem to a twodimensional problem. In addition, it minimizes the number of twodimensional problems. This method is very useful for studying multiple inelastic scattering., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cooperia oncophora is one of the most common intestinal nematodes in cattle. It is also the dose-limiting species for the most frequently used anthelmintics, and consequently, the species usually involved in reports of anthelmintic resistance. However, little information is available on its population dynamics, hindering the parameterisation of transmission models to support understanding of the impact of anthelmintic resistance, climate change and alternative control strategies on nematode epidemiology. This systematic review and meta-analysis provides estimates for key life history traits of the parasitic phase of C. oncophora and investigates potential influences of acquired immunity on these traits., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We comment on a Short Communication recently published in Ultramicroscopy in which Brown et al. criticize our description of the time sequence of events in the development of aberration correction systems in electron optics during the 1990s put forward in the introduction to the Ultramicroscopy April 2015 Special Issue. We present an analysis of the published literature furnishing evidence that our description is correct., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Donor-derived bacterial infection is a recognized complication of solid organ transplantation (SOT). The present report describes the clinical details and successful outcome in a liver transplant recipient despite transmission of methicillin-resistant Staphylococcus aureus (MRSA) from a deceased donor with MRSA endocarditis and bacteremia. We further describe whole genome sequencing (WGS) and complete de novo assembly of the donor and recipient MRSA isolate genomes, which confirms that both isolates are genetically 100% identical. We propose that similar application of WGS techniques to future investigations of donor bacterial transmission would strengthen the definition of proven bacterial transmission in SOT, particularly in the presence of highly clonal bacteria such as MRSA. WGS will further improve our understanding of the epidemiology of bacterial transmission in SOT and the risk of adverse patient outcomes when it occurs., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In order to achieve the highest resolution in aberration-corrected (AC) high-resolution transmission electron microscopy (HRTEM) images, high electron doses are required which only a few samples can withstand. In this paper we perform dose-dependent AC-HRTEM image calculations, and study the dependence of the signal-to-noise ratio, atom contrast and resolution on electron dose and sampling. We introduce dose-dependent contrast, which can be used to evaluate the visibility of objects under different dose conditions. Based on our calculations, we determine optimum samplings for high and low electron dose imaging conditions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We present model-based image simulations for zero-loss and plasmon-loss filtered images at 20 kV for graphene and silicon based on the mutual coherence approach. In addition, a new approximation for the mixed dynamic form factor is introduced. In our calculation multiple elastic scattering and one inelastic scattering are taken into account. The simulation shows that even the intensity of zero-loss filtered image is attenuated by the interference between inelastically scattered waves. Moreover, the intensity of plasmon-loss filtered images cannot be neglected, either., (© 2013 Elsevier B.V. All rights reserved.)

Objectives: HIV infection is associated with dyslipidaemia and increased risk of cardiovascular disease. The effects of HIV infection and antiretroviral treatment on surrogate markers of atherosclerosis, and lipoprotein metabolism were evaluated in a 12 month prospective study., Methods and Results: Treatment-naive HIV patients were recruited into one of three groups: untreated HIV infection not likely to require initiation of antiretroviral therapy (ART) for at least 12 months; initiating treatment with non nucleoside reverse transcriptase inhibitor-containing ART regimen and initiating treatment with protease inhibitor-containing ART regimen. The patients underwent assessment of carotid intima-media thickness (cIMT), pulse wave velocity (PWV), brachial flow-mediated dilation (FMD) and variables of plasma lipoprotein metabolism at baseline and 12 months. The findings were compared with published values for age and sex matched HIV-negative healthy subjects in a cross-sectional fashion. cIMT and FMD were lower while PWV was higher in HIV-patients compared with HIV-negative individuals; none of the markers changed significantly during 12 months follow up. HIV patients had hypoalphalipoproteinemia and elevated plasma levels of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein. The only significant changes in lipid-related variables were elevation of total cholesterol and triglycerides in patients treated with PI-containing regimen and elevation of plasma LCAT levels in patients treated with NNRTI-containing regimen. The ability of whole and apoB-depleted plasma to effect cholesterol efflux was not impaired in all three groups., Conclusions: This study did not find evidence for rapid progression of subclinical atherosclerosis and deterioration of dyslipidaemia in HIV patients within 1 year., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Any torsion experienced at a fracture site will directly translate into shearing forces and has been regarded as detrimental to healing. The purpose of this study was to determine which plating system currently on the market controls torsional forces about comminuted olecranon fractures most effectively., Methods: Five olecranon plates (Acumed, Synthes-SS, Synthes-Ti, ITS/US Implants and Zimmer) were implanted to stabilise a simulated comminuted fracture pattern in 50 fresh-frozen, cadaveric elbows. All specimens were evaluated by dual energy X-ray absorptiometry (DXA) scan to determine bone density. Three-dimensional displacement analysis was conducted to assess fragment motion through physiologic cyclic arcs of motion. The specimens were cycled through progressive physiologic loads (0.18-5.6 kg). Movements of the fragments were statistically compared amongst the different implants using one-way analysis of variance (ANOVA) and Tukey Honestly Significant Difference (HSD) post hoc comparisons with a critical significance level of α=0.05., Results: DXA bone mineral densities (BMDs) ranged from 0.465 to 0.927, with an average of 0.714. The Acumed, Synthes-SS, Synthes-Ti and Zimmer plates allowed <1° of torsion up to 1.6 kg of load. The differences between these plates at this load were not statistically significant. The ITS/US Implants plate, however, allowed significantly more torsion above loads of 2.6 kg (p=0.045) compared with all other plates. The ITS/US Implants plate allowed over 2° of torsion at 2.6 kg (p=0.012), and nearly 3° at 3.6 kg (p=0.045). The Zimmer plate consistently allowed more torsion than the Acumed plate or either of the Synthes plates, but the differences were not statistically significant., Conclusion: Regardless of which olecranon plate is used, the authors recommend limiting postoperative rehabilitation loads to below 1.6 kg in an effort to minimise the detrimental effects of torsion on healing. If loads over 1.6 kg are anticipated, the authors recommend the use of the Acumed plate or either of the Synthes plates., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The dependence of high-resolution transmission electron microscopy (HRTEM) image contrast of graphene on the adjustable parameters of an aberration-corrected microscope operated at 80 and 20 kV has been calculated and, for 80 kV, compared with measurements. We used density functional theory to determine the projected atom potential and obtained the image intensity by averaging over the energy distribution of the imaging electrons, as derived from the electron energy loss spectroscopy measurements. Optimum image contrast has been determined as a function of energy spread of the imaging electrons and chromatic aberration coefficient, showing that significant improvement of contrast can be achieved at 80 kV with the help of a monochromator, however at 20 kV only with chromatic aberration correction and bright atom contrast conditions., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The prevalence of livestock ectoparasites is the result of a complex interaction of factors such as parasite and host abundance, host susceptibility, climate and, critically, farmer husbandry and intervention strategies, all of which change seasonally in space and time. Given the complexity of the interacting factors, the effects of any climate change on disease incidence are hard to predict, as accordingly are the optimal husbandry responses required to ameliorate any effects. Here cutaneous myiasis in sheep, by the blowfly Lucilia sericata in the United Kingdom, is used to highlight the impact of a range of such issues. Cutaneous myiasis would be expected to be highly sensitive to even small changes in climate and therefore provides a good model to illustrate the problems inherent in attempting to predict the effect of climate change on livestock disease incidence. Both simulation and spatial species distribution models, show that the range of elevated temperatures predicted by current climate change scenarios are likely to result in an elongated blowfly season with earlier spring emergence and a higher cumulative incidence of strike. Strike incidence would be expected to increase, particularly for ewes in early summer. However, under higher IPCC emissions senarios (+3 °C), parts of central and southern England may become too hot and dry for strike by L. sericata to persist in mid-summer. Under these conditions, it is possible that other, more pathogenic Mediterranean agents of myiasis, such as Wohlfahrtia magnifica could replace L. sericata. Nevertheless, the models suggest that simple changes in some husbandry practices, such as shearing or trap use, could have an important effect in reducing early season ewe strike incidences by L. sericata. The work reviewed here, suggests that climate warming is likely to increase the risk of fly strike incidence, with consequent animal welfare and economic problems. However, practical measures exist which, with modest changes in husbandry practices, should be able to manage expected increases in strike, under the range of climate changes currently predicted. The work demonstrates that attempts to predict the likely impact of climate change on disease incidence must take into account changes in farmer behaviour and animal management practices as well as parasite biology., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Lake Chapala is a major source of water for crop irrigation and subsistence fishing for a population of 300,000 people in central Mexico. Economic activities have created increasing pollution and pressure on the whole watershed resources. Previous reports of mercury concentrations detected in fish caught in Lake Chapala have raised concerns about health risks to local families who rely on fish for both their livelihood and traditional diet. Our own data has indicated that 27% of women of childbearing age have elevated hair mercury levels, and multivariable analysis indicated that frequent consumption of carp (i.e., once a week or more) was associated with significantly higher hair mercury concentrations. In this paper we describe a range of environmental health research projects. Our main priorities are to build the necessary capacities to identify sources of water pollution, enhance early detection of environmental hazardous exposures, and deliver feasible health protection measures targeting children and pregnant women. Our projects are led by the Children's Environmental Health Specialty Unit nested in the University of Guadalajara, in collaboration with the Department of Environmental Health of Harvard School of Public Health and Department of Pediatrics of the New York School of Medicine. Our partnership focuses on translation of knowledge, building capacity, advocacy and accountability. Communication will be enhanced among women's advocacy coalitions and the Ministries of Environment and Health. We see this initiative as an important pilot program with potential to be strengthened and replicated regionally and internationally., (Published by Elsevier Inc.)

The electron optical performance of a transmission electron microscope (TEM) is characterized for direct spatial imaging and spectroscopy using electrons with energies as low as 20 keV. The highly stable instrument is equipped with an electrostatic monochromator and a C(S)-corrector. At 20 kV it shows high image contrast even for single-layer graphene with a lattice transfer of 213 pm (tilted illumination). For 4 nm thick Si, the 200 reflections (271.5 pm) were directly transferred (axial illumination). We show at 20 kV that radiation-sensitive fullerenes (C(60)) within a carbon nanotube container withstand an about two orders of magnitude higher electron dose than at 80 kV. In spectroscopy mode, the monochromated low-energy electron beam enables the acquisition of EELS spectra up to very high energy losses with exceptionally low background noise. Using Si and Ge, we show that 20 kV TEM allows the determination of dielectric properties and narrow band gaps, which were not accessible by TEM so far. These very first results demonstrate that low kV TEM is an exciting new tool for determination of structural and electronic properties of different types of nano-materials., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Changes in the cortisol awakening response (CAR) were studied in women participating in a Mindfulness-Based Stress Reduction (MBSR) program after completion of their medical treatment for breast cancer., Method: Thirty-three women completed questionnaires pre- and post-MBSR pertaining to: stress, depressive symptomatology, and medical symptoms. The CAR was assessed on 3 days pre- and 3 days post-MBSR as a biological marker of stress., Results: A significant effect on the CAR was found, with cortisol levels showing a prolonged increase after awakening at the post-MBSR assessment period. This was accompanied by significant improvements in self-reported stress levels, depressive symptomatology, and medical symptoms. Furthermore, the change in medical symptoms was negatively correlated with the area under the curve (AUC) at study onset (r = -.52, p < .002); i.e., the greater the AUC of the CAR before MBSR, the greater the reduction in medical symptoms after the program., Conclusions: These results suggest the potential usefulness of employing the CAR as a biological marker in women with breast cancer participating in an MBSR program., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The lateral resolution of a surface sensitive low-energy electron microscope (LEEM) has been improved below 4 nm for the first time. This breakthrough has only been possible by simultaneously correcting the unavoidable spherical and chromatic aberrations of the lens system. We present an experimental criterion to quantify the aberration correction and to optimize the electron optical system. The obtained lateral resolution of 2.6 nm in LEEM enables the first surface sensitive, electron microscopic observation of the herringbone reconstruction on the Au(111) surface., (Copyright 2010 Elsevier B.V. All rights reserved.)

The theoretical aspects of image formation in the transmission electron microscope (TEM) are outlined and revisited in detail by taking into account the elastic and inelastic scattering. In particular, the connection between the exit wave and the scattering amplitude is formulated for non-isoplanatic conditions. Different imaging modes are investigated by utilizing the scattering amplitude and employing the generalized optical theorem. A novel obstruction-free anamorphotic phase shifter is proposed which enables one to shift the phase of the scattered wave by an arbitrary amount over a large range of spatial frequencies. In the optimum case, the phase of the scattered wave and the introduced phase shift add up to -pi/2 giving negative contrast. We obtain these optimum imaging conditions by employing an aberration-corrected electron microscope operating at voltages below the knock-on threshold for atom displacement and by shifting optimally the phase of the scattered electron wave. The optimum phase shift is achieved by adjusting appropriately the constant phase shift of the phase plate and the phase shift resulting from the defocus and the spherical aberration of the corrected objective lens. The realization of this imaging mode is the aim of the SALVE project (Sub-A Low-Voltage Electron microscope)., (Copyright 2009 Elsevier B.V. All rights reserved.)

While much attention has been devoted to examining the beneficial effects of Mindfulness-Based Stress Reduction programs on patients' ability to cope with various chronic medical conditions, most studies have relied on self-report measures of improvement. Given that these measures may not accurately reflect physiological conditions, there is a need for an objective marker of improvement in research evaluating the beneficial effects of stress management programs. Cortisol is the major stress hormone in the human organism and as such is a promising candidate measure in the study of the effects of Mindfulness-Based Stress Reduction programs. In conjunction with other biological measures, the use of cortisol levels as a physiological marker of stress may be useful to validate self-reported benefits attributed to this program. In the current manuscript, we review the available literature on the role of cortisol as a physiological marker for improvement with regards to mindfulness practice, and make recommendations for future study designs., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Psoroptic mange in sheep, resulting from infestation by the astigmatid mite Psoroptes ovis, is increasingly prevalent in Europe and other parts of the world. As a step towards improved national control, regional or local scab management programmes that target high-risk areas and aim to maintain the number of outbreaks below an acceptable level may be an effective initial use of time and resource. To facilitate such a management approach, in this paper scab outbreak farms are identified using a questionnaire survey of sheep farmers, the data from which are then used to build a national scab risk model for Great Britain. The questionnaire results indicate a national prevalence of scab, between March 2007 and February 2008, of 8.6% (+/-1.98). However, previous exposure to sheep scab significantly affected the respondent's probability of reporting a scab outbreak during the survey period (chi(2)=53.2, d.f.=1, P<0.001); 85% of the farms that reported at least one scab outbreak had experienced outbreaks in previous years, 27% had experienced outbreaks in more than five of the previous 10 years. In contrast, 76% of farms that did not report scab had not had a previous outbreak. The highest prevalence areas were in Northern England, Wales, Southwest England and Scotland. Modelling the distribution of the reported scab outbreaks identified height above sea level, temperature and rainfall as significant predictors of the probability of an outbreak, superimposed on an underlying pattern of sheep abundance. It is argued that scab management programmes directed at these foci have the potential to allow a more targeted approach to scab control and significantly reduce the prevalence of scab in the UK and other European countries.

Objective: HIV infection is associated with elevated risk of cardiovascular disease. The effect of antiretroviral drugs on metabolism of atherogenic very low and low density lipoproteins is well studied, but a possible effect of these drugs on reverse cholesterol transport is still unclear. The objective of this study was to assess the effect of various classes of anti-HIV drugs on cellular cholesterol efflux., Methods: The effect of pharmacological concentrations of seven commonly used antiretroviral compounds, Stavudine, Efavirenz, Nevirapine, Lopinavir, Amprenavir, Nelfinavir and Ritonavir, on cholesterol efflux from RAW 264.7 mouse macrophages and human monocyte-derived macrophages to apolipoprotein A-I and high density lipoprotein was tested., Results: At high pharmacological concentration Nelfinavir and Ritonavir inhibited cholesterol efflux, while other compounds had no effect. However, the same concentrations of Nelfinavir and Ritonovir induced apoptosis, suggesting that the effect of these compounds on cholesterol efflux most likely resulted from their cytotoxicity. When tested in non-cytotoxic concentrations, Nelfinavir and Ritonavir did not affect cholesterol efflux from RAW 264.7 cells, human monocyte-derived macrophages, or human macrophages infected with HIV-1., Conclusions: We conclude that tested antiretroviral compounds do not have a specific effect on cholesterol efflux.

Enzyme-catalysed degradation of the nerve agents tabun, sarin, ethyl sarin and soman by three variants of an organophosphate-degrading enzyme was studied at low concentrations of nerve agent. The concentration of nerve agent at a given time was determined by its ability to inhibit the enzyme acetylcholinesterase. Experiments were conducted in 96-well microtitre plates. Values of the ratio of k(cat) (turnover number) to K(m) (Michaelis-Menten constant) were calculated. For tabun, this value (for the most effective OpdA variant) exceeded any value published to date for other enzymes. The value was within an order of magnitude for the highest value reported for sarin, but there appears to be no published value for ethyl sarin for comparison. The OpdA enzymes were relatively inefficient in degrading soman.

HIV infection and its treatment are associated with dyslipidemia, including hypoalphalipoproteinemia, and increased risk of cardiovascular disease. Parameters of HDL metabolism in HIV-positive patients were investigated in a cross-sectional study. The following groups of subjects were selected: (i) 25 treatment-naïve HIV-infected patients or HIV-infected patients on long therapy break, (ii) 28 HIV-infected patients currently treated with protease inhibitors, and (iii) 33 HIV-negative subjects. Compared to the HIV-negative group, all groups of HIV-infected patients were characterized by significantly elevated triglyceride and apolipoprotein B levels, mass and activity of lecithin cholesterol acyl transferase and cholesteryl ester transfer protein (p<0.01). Total and LDL cholesterol was lower in treatment-naïve HIV-infected group only. HDL cholesterol and prebeta(1)-HDL were significantly lower in all HIV-infected groups (p<0.05), while mean levels of apolipoprotein A-I (apoA-I) and ability of plasma to promote cholesterol efflux were similar in all groups. We found a positive correlation between apoA-I and levels of CD4+ cells (r(2)=0.3, p<0.001). Plasma level of phospholipid transfer protein was reduced in the group on antiretroviral therapy. Taken together these results suggest that HIV infection is associated with modified HDL metabolism re-directing cholesterol to the apoB-containing lipoproteins and likely reducing the functionality of reverse cholesterol transport.

Future aberration-corrected electron microscopes that will enable sub-Angstroem spatial and sub-eV energy resolution are outlined . The sub-Angstroem transmission electron microscope (SATEM) only compensates for the spherical aberration and reduces the chromatic aberration disc by means of a monochromator. In order to correct for both aberrations, two novel correctors, the ultracorrector and the superaplanator are proposed which will yield a resolution limit of about 0.5A and a large field of view of more than 4 x 10(6) image points. The superaplanator is best suited for obtaining an achromatic aplanat required for the realization of the high-performance in situ electron microscope of the TEAM project.

A detailed theoretical formulation of the primary and secondary chromatic aberrations of electron-optical systems with a straight optic axis is outlined. To simplify the mathematical expenditure only systems composed of magnetic round lenses and magnetic and electrostatic quadrupoles are taken into account. By appropriately arranging these elements, it is possible to construct feasible electron-optical analogues of light-optical achromats and apochromats.

Background: Glycation reactions of proteins and other compounds, depending on blood glucose concentrations, have a detrimental effect on health., Objective: The association of diet and other lifestyle factors with glycated hemoglobin (Hb A(1c)) values was examined in a nondiabetic population., Design: This was a cross-sectional study of 1773 middle-aged men and women. Mean Hb A(1c) values were calculated for categories of diet and lifestyle factors, and odds ratios (ORs) for the highest versus lowest tertiles of Hb A(1c) were determined and compared., Results: The OR of being in the highest Hb A(1c) tertile compared with the lowest increased with greater age [age 40-44 y compared with >60 y: men (OR: 2.86; 95% CI: 1.60, 5.20) and women: (6.11; 3.15, 12.30)] and greater obesity [body mass index (in kg/m(2)) >25 and waist-hip ratio >1.0 in men and >0.8 in women): men (2.80; 1.48, 5.45) and women (1.73; 1.15, 2.61)]. High energy and energy-adjusted saturated fat intakes were associated with increased risk of being in the highest tertile of Hb A(1c) [highest compared with lowest quintile: (1.53; 1.04, 2.26; P for trend = 0.013) and (1. 98; 1.33, 2.95; P for trend = 0.003), respectively]. No significant associations were observed for intakes of carbohydrates, protein, dietary fiber, or beta-carotene; however, some of the associations were nearly significant. Alcohol, vitamin C, and vitamin E intakes were inversely related to risk [highest compared with lowest quintile: (0.56; 0.38, 0.83; P for trend = 0.001), (0.50; 0.33, 0. 74; P for trend = 0.003), and (0.65; 0.43, 0.96; P for trend = 0. 036), respectively]., Conclusion: Hb A(1c) values might be modifiable by diet and other lifestyle factors.

The paper describes the application of liquid chromatography interfaced to a triple quadrupole mass spectrometer utilising the multiple reaction monitoring (MRM) mode. The technique was shown to provide detection limits lower than 0.01% for the analysis of prednisone in the presence of hydrocortisone. Prednisone was mixed in concentrations from 0.500 to 0.0005 ppm (corresponding to 1% to 0.001% of the hydrocortisone concentration). These solutions were assayed using MRM observing the product ion transitions of 359.2-->147.1 and 359.2-->171.2 and was shown to be capable of detecting co-eluting impurities at concentrations of less than 0.001% of the major component. The assay of prednisone was shown to be linear over the range 0.500-0.0005 ppm with a correlation coefficient of 0.999 and a precision of 6.9% at the concentration of 0.005 ppm. The analysis was carried out using both atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI) as an interface. However, for these compounds APCI provided significantly more sensitive data compared to ESI.

Several pesticides used as herbicides, insecticides and fungicides are known to be endocrine disrupting chemicals (EDCs). In three pair-matched studies we found changes in sex hormone concentrations and T-lymphocytes in relation to acute and chronic pesticide exposure. After acute exposure, 1 day later the concentrations of testosterone and especially estradiol decreased. T4- and T8-lymphocytes slightly increased. Effects of chronic occupational pesticide exposure were expressed by a higher level of testosterone and a larger ratio of T4-/T8-lymphocytes in comparison to control persons. Concentrations of LH in exposed men were higher after exposure than before. We assume an inhibition of the aromatase system by testosterone metabolites. The studies show two effects with regard to the duration of exposure: a hormonal and immune suppression after acute exposure and an activation of both systems following chronic exposure.

The action of anoxia on glucose transport was investigated in isolated resting rat cardiomyocytes. Incubation of these cells in the absence of oxygen for 30 min resulted in a 4- to 5-fold increase in glucose transport (with a lag period of 5-10 min). Up to 40 min of anoxia failed to alter the cellular concentrations of ATP, phosphocreatine, and creatine. Adenosine deaminase (1.5 U/ml), the A1-adenosine receptor antagonist 1,3-diethyl-8-phenylxanthine (1 microM), or the A2-selective antagonist 3,7-dimethyl-1-propargylxanthine (20 microM) had no effect on anoxia-dependent glucose transport. Moreover, adenosine (10-300 microM, added under normoxia) did not stimulate glucose transport. Wortmannin (1 microM) did not influence the effect of anoxia, but completely suppressed that of insulin. On the other hand, the effects of anoxia and insulin were not additive. These results indicate (i) that the effect of anoxia on cardiomyocyte glucose transport is not mediated by a change in energy metabolism, nor by an adenosine release; (ii) that it probably does not involve a phosphatidylinositol 3-kinase, in contrast to the effect of insulin, and (iii) that the signal chains triggered by anoxia or insulin may converge downstream of this enzyme, or, alternatively, that anoxic conditions may impair the action of the hormone.